Actualización sobre los medicamentos biocomparables en la enfermedad inflamatoria intestinal: posición y recomendación en México

The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons.The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.     

Multidisciplinary management of the nocebo effect in biosimilar-treated IBD patients: Results of a workshop from the NOCE-BIO consensus group

The high cost of biological drugs for patients with inflammatory bowel disease (IBD) considerably impacts on health-care budgets. Since the patent of biological products expired, cheaper biosimilars have entered the market. Available data coming from real-world cohorts and clinical trials indicate that the efficacy and safety of biosimilars is comparable to that of the originator drugs. Treating IBD patients with a biosimilar may be complicated by the risk of the nocebo effect, a negative effect of a pharmacological or non-pharmacological treatment, induced by patients’s expectations and unrelated to the physiological action of the treatment. The nocebo effect can negatively affect treatment outcomes and hamper the cost-savings of biosimilars. Reducing the nocebo effect requires a multidisciplinary effort of all health-care providers in charge of biosimilar-treated IBD patients. The aim of the review is to reflect the key messages of an international workshop on this topic, including viewpoints from the perspective of physicians, nurses, psychologists, pharmacists and patients.     

Biosimilars in paediatric inflammatory bowel disease

The introduction of biological treatments has changed disease outcomes for patients with inflammatory bowel disease. Biologicals have high efficacy, and can induce and maintain remission after failed responses to conventional immunosuppressive and/or steroid therapy. The increasing occurrence of severe disease at diagnosis has resulted in infliximab being more often introduced as the firstline treatment in a "top-down" approach. Besides their favourable efficacy and safety profile, biologicals have one significant disadvantage, which is their high cost. This results in many patients stopping therapy prematurely, with the maintenance phase being too short. This often leads to disease exacerbation shortly after treatment cessation. Every newly started course of biological therapy can induce production of anti-drug antibodies, which can result in treatment failure and possible allergic/anaphylactic reactions. The introduction of biological biosimilars was intended to greatly reduce therapy costs thus increasing the availability of these agents to more patients. It was also anticipated that biosimilars would prevent premature termination of therapy. Analyses of paediatric data suggest that biosimilar infliximabs are equally effective as the reference infliximab. Safety patterns also seem to be similar. Paediatric experience places costtherapy reductions at around 10%-30%.     

Does Similarity Breed Contempt? A Review of the Use of Biosimilars in Inflammatory Bowel Disease

The introduction of therapeutic monoclonal antibodies directed against tumor necrosis factor-α has revolutionized the treatment of inflammatory bowel disease (IBD) by improving quality of life, decreasing the frequency and length of hospital admissions, and reducing corticosteroid use. Nevertheless, biologics are very expensive, substantially contributing to the cost of care for patients with IBD. To reduce this cost and improve treatment access, biosimilars, which are therapeutic monoclonal antibodies (biologicals) similar to but not identical to the reference biologic, were introduced. Despite their potential benefits, the adoption and uptake of biosimilars have varied considerably across the USA and Europe. Here, we highlight the current biosimilar therapeutic landscape, discuss barriers to their use, and provide an overview of published studies evaluating the efficacy and safety of biosimilars in IBD.

     

Biosimilars in immune‐mediated inflammatory diseases: initial lessons from the first approved biosimilar anti‐tumour necrosis factor monoclonal antibody

The introduction of targeted biological therapies has revolutionised the management of immune‐mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of ‘biosimilar’ drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost‐effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the ‘switchability’ and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT‐P13, a biosimilar of the anti‐tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed.     

Biosimilars for inflammatory bowel disease: how can healthcare professionals help address patients’ concerns?

Introduction: The patent expiration of some biologics used in chronic conditions such as inflammatory bowel disease (IBD) has led to the development of biosimilar monoclonal antibodies. The tailored regulatory approval route for biosimilar development ensures that approved biosimilars show similarity to their originators in terms of efficacy and safety, and avoids unnecessary repetition of clinical trials carried out with the originator product. However, some patients may still have concerns about using biosimilars and it is the responsibility of healthcare professionals (HCPs) to alleviate these concerns.

Areas covered: This review highlights clinical and real-world evidence supporting efficacy and safety of biosimilars in patients with IBD. Moreover, based on international surveys, potential patient concerns are highlighted, along with possible actions HCPs can take to address these concerns.

Expert commentary: The rising use of biosimilars in IBD is expected to have a positive impact on the availability of biologics and healthcare costs. Several biosimilars have been approved for use and more are likely to come to the market in the future; however, transitioning patients to biosimilars could pose an unexpected challenge without the help and support of HCPs.     

Biosimilars in inflammatory bowel disease: A review of post-marketing experience

Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods.A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined "boundaries of tolerance": differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited.     

Novedades sobre los tratamientos para la enfermedad inflamatoria intestinal

Several studies on conventional drugs and new treatments in inflammatory bowel disease were presented in Digestive Disease Week 2013. Various studies have compared infliximab and cyclosporin in corticosteroid-refractory ulcerative colitis in clinical practice, providing complementary information to the CYSIF clinical trial. For the first time, a clinical trial has evaluated the efficacy of adalimumab in preventing recurrence of Crohn's disease after surgery. The results of some studies suggest that thiopurines improve response to infliximab, in both Crohn disease and ulcerative colitis. Finally, several studies were presented on new drugs with new therapeutic targets, such as vedolizumab, in the treatment of inflammatory bowel disease. The preliminary results of the ASTIC trial were reported, which evaluated the safety and efficacy of bone marrow transplantation in Crohn's disease.     

Emerging biologics in inflammatory bowel disease

Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries. A number of new therapeutic targets, including novel small molecules, and cellular therapy are available or under investigation. These novel molecules include oral Janus kinase (JAK) inhibitor (tofacitinib), interleukin inhibitor (ustekinumab), oral SMAD7 antisense oligonucleotide (mongersen), and anti-integrin inhibitors (vedolizumab). Here, we review the mechanisms of action, the efficacy, and the safety data of these novel agents. Biological products that are highly similar to reference biologic products whose patents have expired—also known as "biosimilars"—can be produced at lower cost with similar efficacy, and are also available for the treatment of IBD. We review the efficacy data for such agents as well.

     

Biosimilars: The viewpoint of Italian patients with inflammatory bowel disease

BackgroundThe viewpoint on biosimilars among patients with inflammatory bowel diseases (IBD) is largely unknown.AimsWe aimed at exploring the confidence and opinion on biosimilars among Italian patients with IBD.MethodsAn anonymous, 20-item, questionnaire was sent via e-mail to all members of the Italian IBD patients‘ association (AMICI Onlus). Three sets of questions were formulated: 1: Characteristics of respondents; 2: The use of biologics and biosimilars in clinical practice; 3: General opinions on biologics and biosimilars.ResultsOf the 4,302 total surveys sent, there were 1,749 respondents (response rate: 40.6%). There was an equal distribution between males and females (48.3% and 51.7%, respectively), and between patients with Crohn's disease and ulcerative colitis (46.9% and 51.3%, respectively), while most of the patients were aged between 19 and 45 years and between 46 and 65 years (45.5% and 42.0%, respectively). Approximately 45% of the respondents declared to have never been informed about the existence of biosimilars. The great majority of patients (73.9%) did not know if originators and biosimilars could be considered equivalent, or if efficacy or safety of biosimilars could be lower than those of originators. Approximately half of the respondents (53.5%) had no idea that the use of low-cost biosimilars could be useful to increase the overall economic resources for the treatment of IBD.ConclusionsAn extensive lack of knowledge and confidence in biosimilars exists among Italian patients with IBD. Efforts carried out by scientific societies and IBD patients’ associations are required to overcome this issue.     

Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine?

The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.     

Anti-TNF biosimilars in Crohn’s Disease: a patient-centric interdisciplinary approach

ABSTRACT

Introduction: The purpose of this review is to highlight the role of biosimilars in early treatment in IBD and introduce ways to facilitate a patient-centric switching process through multidisciplinary approach.

Areas covered: We summarize existing scientific literature related to the role of biosimilars in inflammatory bowel disease in terms of early treatment and cost-saving and implementing switching process.

Expert opinion: Use of anti-TNF biosimilars in patients has the potential for large drug-acquisition cost-saving, which can be reinvested into early treatment. Managed switched programs for adalimumab can add further benefits in the future.     

Use of thiopurines in inflammatory bowel disease: Safety issues

Thiopurines are widely used for maintenance treatment of inflammatory bowel disease. Interindividual variability in clinical response to thiopurines may be attributed to several factors including genetic polymorphisms, severity and chronicity of disease, comorbidities, duration of administration, compliance issues and use of concomitant medication, environmental factors and clinician and patient preferences. The purpose of this review is to summarise the current evidence on thiopurine safety and toxicity, to describe adverse drug events and emphasise the significance of drug interactions, and to discuss the relative safety of thiopurine use in adults, elderly patients, children and pregnant women. Thiopurines are safe to use and well tolerated, however dose adjustment or discontinuation of treatment must be considered in cases of non-response, poor compliance or toxicity. Drug safety, clinical response to treatment and short to long term risks and benefits must be balanced throughout treatment duration for different categories of patients. Treatment should be individualised and stratified according to patient requirements. Enzymatic testing prior to treatment commencement is advised. Surveillance with regular clinic follow-up and monitoring of laboratory markers is important. Data on long term efficacy, safety of thiopurine use and interaction with other disease modifying drugs are lacking, especially in paediatric inflammatory bowel disease. High quality, collaborative clinical research is required so as to inform clinical practice in the future.     

Some cases demonstrating the clinical usefulness of therapeutic drug monitoring in thiopurine-treated inflammatory bowel disease patients

The thiopurines azathioprine and 6-mercaptopurine (6-MP) are effective drugs in steroid-dependent and refractory inflammatory bowel disease patients. Therapeutic drug monitoring (TDM) is a new concept to improve drug efficacy and prevent toxic adverse events. As thiopurine metabolism is influenced by genetic polymorphisms of methylating enzymes, metabolite levels may vary considerably, enabling significant adverse effects. In the present paper five patients are described to demonstrate the clinical usefulness of TDM when applying thiopurines for inflammatory bowel disease. Emphasized are patients with liver function test abnormalities and myelosuppression due to inappropriate 6-MP metabolite levels, and subsequently the treatment of these events. In addition, sophisticated 6-MP metabolite level-guided therapy, including non-compliance, is demonstrated. These cases demonstrate that TDM may improve effectivity and safety of thiopurine treatment.     

Novedades sobre la eficacia,optimización y seguridad de los tratamientos de la enfermedad inflamatoria intestinal

In Digestive Disease Week 2012, numerous studies were presented on the treatment, monitoring and safety of drugs in inflammatory bowel diseases. New indications for previously approved treatments were evaluated, mainly in perianal disease and the prevention of postsurgical recurrence. New data were provided on biological markers that could help in the follow-up of patients with inflammatory bowel disease. Several studies were presented on the safety of thiopurine drugs and anti-tumor necrosis factor (TNF) agents during pregnancy. However, much of the meeting was centered on studies determining levels of anti-TNF agents and antibodies against them, evaluating new techniques with greater accuracy in determining levels of these agents and antibodies against them, their correlation with clinical response and their utility in optimizing the treatment of patients with inflammatory bowel disease.     

Biosimilars in the Treatment of Inflammatory Bowel Disease: Supporting Evidence in 2017

Purpose of Review

Monoclonal antibodies targeting tumor necrosis factor-alpha, integrin molecules, and interleukin-12/23 have become backbone therapies for Crohn’s disease and ulcerative colitis. While clinically effective, these biologic therapies come with significant expense, contributing to overall healthcare spending in the USA. Biosimilars have the potential to significantly reduce expenditures secondary to the use of biologic medications such as infliximab and adalimumab, though their complicated manufacturing process results in inherent differences in structure when compared to the originator compounds. In this article, we review the available literature regarding biosimilars in IBD.

Recent Findings

Several biosimilar agents to infliximab and adalimumab are currently FDA-approved, with many more currently in development. Initial clinical trials for approval have been conducted in one of the original indications for each originator biologic. There are growing data demonstrating similar clinical efficacy, immunogenicity, and safety of each of the approved infliximab and adalimumab biosimilars, both through indication extrapolation from other diseases such as rheumatoid arthritis and ankylosing spondylitis, as well observational data in patients with inflammatory bowel disease. Further research is ongoing regarding the efficacy and safety of substitution and interchangeability of biosimilars, as well as therapeutic drug monitoring for biosimilar agents.

Summary

Research to date supports the utilization of reference biologics and biosimilars for new initiators, while additional data are being accrued regarding the interchangeability between these agents.

     

Azathioprine or 6-mercaptopurine for inflammatory bowel disease: do risks outweigh benefits?

The treatment of Crohn's disease and ulcerative colitis has evolved and has improved the quality of life of patients afflicted with these disorders. Immune modulators such as azathioprine and 6-mercaptopurine are an important class of medications used for the treatment of patients with inflammatory bowel disease. Controlled studies have demonstrated their efficacy in both induction and maintenance of remission in Crohn's disease, and similarly, for the induction and maintenance of remission in patients with ulcerative colitis. These agents have had an increasing importance in the management of steroid-resistant, steroid-dependent diseases, and fistulizing Crohn's disease. The primary limitations to these agents have been their slow onset of action and their side effect profile. Despite these limitations, these agents have demonstrated efficacy and have become paramount to the management of patients with these incurable potentially disabling disorders. The precise role of azathioprine/6-mercaptopurine, their limitations and their safety are reviewed in this paper.     

AINE,toxicidad gastrointestinal y enfermedad inflamatoria intestinal

Non-steroidal antiinflammatory drugs (NSAIDs) are currently one of the most widely used drugs. The use of NSAIDs is associated with gastrointestinal toxicity, affecting both upper gastrointestinal tract (peptic ulcer disease) and lower gastrointestinal tract (NSAID-induced enteropathy).NSAIDs use has been associated with an increased risk of clinical relapse in inflammatory bowel disease patients. In this article, we review the upper and lower gastrointestinal toxicity of NSAIDs, with a focus on the risks and specific data of these drugs in inflammatory bowel disease patients, giving recommendations for its appropriate use in the clinical practice. Although evidence is scarce, short-term use of NSAIDs appears to be safe, and the data available suggest that selective COX-2 inhibitors are the safer option. NSAIDs should be avoided as long-term treatment or with high doses, especially in patients with active inflammation.     

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge.